Abstract
Transgenic mice that allow targeting of SV40 T antigen (Tag) to the prostate provide a unique model to identify cancer-initiating cells and follow their progression from a normal cell phenotype into prostate cancer cells. We have developed the FG/Tag transgenic mouse model of prostate cancer using the human fetal globin (FG) promoter linked to Tag. Immunohistochemistry results show that before the development of prostate intraepithelial neoplasia (PIN), a subset of p63+ basal epithelial cells expresses Tag. As in the case of human prostate cancer, there is a loss of p63+ basal cells with neoplastic progression, and a long period of time is required for PIN lesions to develop into palpable prostate tumors. Other immunohistochemistry results show cellular heterogeneity in FG/Tag PIN lesions and primary tumors with neuroendocrine differentiation. Cell lines derived from primary prostate tumors showed characteristics of a neuroendocrine-epithelial intermediate cell type. The FG promoter has high transcriptional activity in intermediate (DU 145, PC-3) and p63+ basal epithelial (LHSR-AR) prostate cancer cells. Therefore, the unexpected development of prostate cancer in the FG/Tag mice may be due to the presence of DNA elements in the FG promoter that can target Tag to specific basal or intermediate cells. We conclude that FG/Tag mouse is a unique model of prostate cancer because the initiating cells are a subset of p63 + basal (possibly stem cells), which may be the true cells of origin for carcinogenesis in aggressive human prostate cancer.
| Original language | English |
|---|---|
| Pages (from-to) | 1171-1179 |
| Number of pages | 9 |
| Journal | Molecular Cancer Research |
| Volume | 5 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 1 2007 |
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ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
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Progression of prostate cancer from a subset of p63-positive basal epithelial cells in FG/Tag transgenic mice. / Reiner, Teresita; De Las Pozas, Alicia; Parrondo, Ricardo; Perez-Stable, Carlos.
In: Molecular Cancer Research, Vol. 5, No. 11, 01.11.2007, p. 1171-1179.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Progression of prostate cancer from a subset of p63-positive basal epithelial cells in FG/Tag transgenic mice
AU - Reiner, Teresita
AU - De Las Pozas, Alicia
AU - Parrondo, Ricardo
AU - Perez-Stable, Carlos
PY - 2007/11/1
Y1 - 2007/11/1
N2 - Transgenic mice that allow targeting of SV40 T antigen (Tag) to the prostate provide a unique model to identify cancer-initiating cells and follow their progression from a normal cell phenotype into prostate cancer cells. We have developed the FG/Tag transgenic mouse model of prostate cancer using the human fetal globin (FG) promoter linked to Tag. Immunohistochemistry results show that before the development of prostate intraepithelial neoplasia (PIN), a subset of p63+ basal epithelial cells expresses Tag. As in the case of human prostate cancer, there is a loss of p63+ basal cells with neoplastic progression, and a long period of time is required for PIN lesions to develop into palpable prostate tumors. Other immunohistochemistry results show cellular heterogeneity in FG/Tag PIN lesions and primary tumors with neuroendocrine differentiation. Cell lines derived from primary prostate tumors showed characteristics of a neuroendocrine-epithelial intermediate cell type. The FG promoter has high transcriptional activity in intermediate (DU 145, PC-3) and p63+ basal epithelial (LHSR-AR) prostate cancer cells. Therefore, the unexpected development of prostate cancer in the FG/Tag mice may be due to the presence of DNA elements in the FG promoter that can target Tag to specific basal or intermediate cells. We conclude that FG/Tag mouse is a unique model of prostate cancer because the initiating cells are a subset of p63 + basal (possibly stem cells), which may be the true cells of origin for carcinogenesis in aggressive human prostate cancer.
AB - Transgenic mice that allow targeting of SV40 T antigen (Tag) to the prostate provide a unique model to identify cancer-initiating cells and follow their progression from a normal cell phenotype into prostate cancer cells. We have developed the FG/Tag transgenic mouse model of prostate cancer using the human fetal globin (FG) promoter linked to Tag. Immunohistochemistry results show that before the development of prostate intraepithelial neoplasia (PIN), a subset of p63+ basal epithelial cells expresses Tag. As in the case of human prostate cancer, there is a loss of p63+ basal cells with neoplastic progression, and a long period of time is required for PIN lesions to develop into palpable prostate tumors. Other immunohistochemistry results show cellular heterogeneity in FG/Tag PIN lesions and primary tumors with neuroendocrine differentiation. Cell lines derived from primary prostate tumors showed characteristics of a neuroendocrine-epithelial intermediate cell type. The FG promoter has high transcriptional activity in intermediate (DU 145, PC-3) and p63+ basal epithelial (LHSR-AR) prostate cancer cells. Therefore, the unexpected development of prostate cancer in the FG/Tag mice may be due to the presence of DNA elements in the FG promoter that can target Tag to specific basal or intermediate cells. We conclude that FG/Tag mouse is a unique model of prostate cancer because the initiating cells are a subset of p63 + basal (possibly stem cells), which may be the true cells of origin for carcinogenesis in aggressive human prostate cancer.
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UR - http://www.scopus.com/inward/citedby.url?scp=36248971056&partnerID=8YFLogxK
U2 - 10.1158/1541-7786.MCR-07-0024
DO - 10.1158/1541-7786.MCR-07-0024
M3 - Article
C2 - 17982114
AN - SCOPUS:36248971056
VL - 5
SP - 1171
EP - 1179
JO - Molecular Cancer Research
JF - Molecular Cancer Research
SN - 1541-7786
IS - 11
ER -